The major cell surface protein of cultured fibroblasts is a large (220,000 dalton) glycoprotein termed CSP. There is a growing body of evidence that CSP is one of the biological macromolecules responsible for orderly cell-cell and cell-substratum interactions and for the maintenance of normal cell morphology. Human lung fibroblasts shed CSP from the cell surface with a half-life of 25 hours. Simultaneous with the loss of CSP from the cell surface, a similar macromolecule appears in the culture medium. This shedding process appears to be stoichiometric. Studies with human neutrophil proteases have demonstrated that human fibroblasts CSP is remarkably sensitive to proteolysis. The small amounts of these proteases will destroy the ability of CSP to agglutinate cells and to attach cells to a collagen substrate. These studies suggest that one of the effects of the inflammatory process is to destroy macromolecules such as CSP such that cellular order is disrupted.